Gene therapy using replication-defective herpes simplex virus vectors expressing nerve growth factor in a rat model of diabetic cystopathy.

Katsumi Sasaki; Michael B Chancellor; William F Goins; Michael W Phelan; Joseph C Glorioso; William C de Groat; Naoki Yoshimura

doi:10.2337/diabetes.53.10.2723

PubMed · 15448108

Gene therapy using replication-defective herpes simplex virus vectors expressing nerve growth factor in a rat model of diabetic cystopathy.

Katsumi Sasaki·Michael B Chancellor·William F Goins·Michael W Phelan·Joseph C Glorioso·William C de Groat·Naoki Yoshimura

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Abstract

Diabetic cystopathy is one of the common complications of diabetes and current therapy is limited. In the present study, the effects of gene therapy, using replication-defective herpes simplex virus type 1 (HSV-1) vectors to deliver and express the nerve growth factor (NGF) gene (HSV-NGF) on tissue NGF levels and bladder function, were evaluated in streptozotocin (STZ)-induced diabetic rats. Diabetic rats exhibited a significant decrease in NGF levels in the bladder and lumbosacral dorsal root ganglia (DRG) detected by enzyme-linked immunosorbent assay and displayed marked bladder dysfunction 12 weeks after STZ injection. In contrast, rats with bladder wall injection of the NGF expression vector 8 weeks after STZ treatment exhibited a significant increase of NGF levels in the bladder and L6 DRG 4 weeks after HSV-NGF injection. Along with the restoration of tissue NGF expression, in metabolic cage studies and cystometry, HSV-NGF-injected rats also showed significantly reduced bladder capacity and postvoid residual volume than diabetic rats injected with the control vector (HSV-lacZ), indicating that voiding function was improved after HSV vector-mediated NGF gene delivery. Thus, HSV vector-mediated NGF gene therapy may prove useful to restore decreased NGF expression in the bladder and bladder afferent pathways, thereby improving hypoactive bladder function in diabetes.

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Animals Defective Viruses Disease Models, Animal Diuresis Female Genetic Therapy Genetic Vectors Nerve Growth Factors Rats Rats, Sprague-Dawley Simplexvirus Urinary Bladder Diseases Journal Article Research Support, U.S. Gov't, P.H.S.

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Katsumi Sasaki, Michael B Chancellor, William F Goins, Michael W Phelan, Joseph C Glorioso, William C de Groat, Naoki Yoshimura. 2004. Gene therapy using replication-defective herpes simplex virus vectors expressing nerve growth factor in a rat model of diabetic cystopathy.. https://doi.org/10.2337/diabetes.53.10.2723

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